title: [A study of conformational states of substrates of cytochrome P450 3A4].
abstract: A multiconformational study of substrates of cytochrome P450 3A4 has been carried out within the BiS/MC algorithm. The method allowed one to create a pseudoatomic model of the cytochrome and to find the substrate conformers responsible for the interaction with the cytochrome. It has been found that, in most cases, the geometry of the acting conformer is much different from the geometry of the global minimum conformer. It has been shown that the mirror conformational antipodes ("enantioconformers") are characterized as a rule by different Michaelis constants. A quantitative relationship between the Michaelis constants and the parameters of interactions in "model 3A4 isoform-substrate" complexes has been determined. The relationship describes the experimental value of Michaelis constant with the squared cross-validation correlation coefficient of 0.88.
authors.forename: M A
authors.initials: MA
authors.lastname: Grishina
authors.forename: V A
authors.initials: VA
authors.lastname: Potemkin
authors.forename: A A
authors.initials: AA
authors.lastname: Pogrebnoĭ
authors.forename: N N
authors.initials: NN
authors.lastname: Ivshina
mesh_terms: D000465:Algorithms; D000818:Animals; D051544:Cytochrome P-450 CYP3A / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013379:Substrate Specificity
chemical_list: D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human